. Complete understanding of the human and other genomes is central to the health of the nation's citizens. A key step in genome analysis is determination of a physical map that allows correct assembly of fragmented sequence information into a continuous genome sequence. The goal of this Phase I SBIR proposal is to test the feasibility of a high throughput, solid state genome mapping method using sequence specific physical tags and AFM. Large target DNA samples (e.g. cosmids or YACs) are tethered to defined addresses on a surface. They are then incubated with sequence specific topographical markers such as catalytically compromised restriction enzymes. The samples are then combed into a linear display, dried and examined by AFM. The AFM quickly generates a topograph of the sample, revealing the positions of the markers along the strand with 30 bp resolution. The advantages of this approach are speed, economy and minimal waste. Further, the order of the sequence tags is immediately known, which is usually not the case with gel-based methods. Finally, the unique attributes of the AFM will facilitate advanced future applications, molecular force-based gene analysis and direct mechanical gene manipulation. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE